The present invention relates to a chiral copper complex, the production process thereof using chiral salicylidene ligands and asymmetric synthesis of cyclopropane-carboxylic acid compound using the complex as a catalyst.
As a process for producing an optically active cyclopropanecarboxylic acid ester derivative, there have been known a process of reacting an olefin with a diazoacetic acid ester in the presence of a certain salicylideneaminoalcohol copper complex catalyst (JP-A 59-225194).
According to the present invention, an industrially suitable chiral copper complex comprising an optically active salicylidenaminoalcohol compound can be readily produced. Said complex is more stable to an oxide that can be contained in a cyclopropanation reaction system, reducing adverse effects of such an oxide and said salicylidenaminoalcohol compound can be recovered after said reaction in an improved yield.
The present invention provides:
1. an optically active salicylideneaminoalcohol compound of formula (1): 
wherein R1 represents
an alkyl group which may be substituted with a group selected from an alkoxy group, an aralkyloxy group, an aryloxy group and cycloalkoxy group,
an aralkyl, aryl or cycloalkyl group all of which may be substituted with a group selected from an alkyl group, an alkoxy group, an aralkyloxy group, an aryloxy roup, and a cycloalkoxy group,
R2 represents
an alkyl group, a cycloalkyl group, or
an aralkyl or phenyl group which may be substituted with a group selected from an alkyl group, an alkoxy group, an aralkyloxy group, an aryloxy group and a cycloalkoxy group,
when X1 represents a nitro, X2 is a hydrogen atom,
when X1 represents a chlorine atom, X2 is a chlorine atom, and
when X1 is a hydrogen atom, X2 is a fluorine atom, and
the carbon atom denoted by xe2x80x9c*xe2x80x9d is an asymmetric carbon atom having either an S or R configuration,
2. a process for producing an optically active salicylideneaminoalcohol compound as defined above, which comprises reacting
an optically active amino alcohol of formula (2): 
wherein R1, R2 and xe2x80x9c*xe2x80x9d have the same meaning s as defined above, with a 2-hydroxybenzaldehyde derivative of formula (3): 
wherein when X1 and X2 are the same as defined above,
3. a chiral copper complex prepared from a mono-valent or di-valent copper compound and an optically active salicylideneaminoalcohol compound (1) as defined above,
4. a method for producing a chiral copper complex of formula (1)xe2x80x2: 
wherein R1 and R2 are the same or different and independently represent an alkyl group, an aralkyl group, a phenyl group, a 2-methoxyphenyl group, a 2-tert-butoxy-5-tert-butylphenyl group, or a 2-octyloxy-5-tert-butylphenyl group;
when X1 represents a nitro group, X2 is a hydrogen atom,
when X1 represents a chlorine atom, X2 is a chlorine atom, and
when X1 represents a hydrogen atom, X2 is a fluorine atom
the carbon atom denoted by xe2x80x9c*xe2x80x9d is an asymmetric carbon atom having either an S or R configuration,
which comprises contacting a di-valent copper compound, in an inert organic solvent, with a chiral salicylideneaminoalcohol compound of formula (1): 
wherein R1, R2 X1, X2 and xe2x80x9c*xe2x80x9d respectively have the same meaning as defined above, and
5. a method for producing an optically active cyclopropane-carboxylic acid ester of formula (4): 
wherein R3, R4, R5, R6 and R7 are as defined below,
which comprises reacting a prochiral olefin of formula (5): 
wherein R3, R4, R5 and R6 are as defined below, with a diazoacetic acid ester of formula (6):
N2CHCO2R7xe2x80x83xe2x80x83(6) 
wherein R7 is as defined below, in the presence of a chiral copper complex as defined in item 3 or 4,
wherein R3, R4, R5 and R6 independently represent
a hydrogen atom,
a halogen atom,
a (C1-C10)alkyl group which may be substituted with a halogen atom or a lower alkoxy group,
a (C4-C8)cycloalkyl group,
an aryl group which may be substituted with a halogen atom or a lower alkoxy group,
an alkoxy group,
R3 and R4, or R5 and R6 may be bonded at their terminals to form an alkylene group having 2-4 carbon atoms, and
one of R3, R4, R5 and R6 groups represents an alkenyl group which may be substituted with a halogen atom, an alkoxy group or an alkoxy carbonyl group, of which alkoxy may be substituted with a halogen atom or atoms,
provided that when R3 and R5 are the same, R4 and R6 are not the same, and
R7 represents an alkyl group having 1 to 8 carbon atoms,
a cycloalkyl group which may be optionally substituted with a lower alkyl group,
a benzyl group which may be optionally substituted with a lower alkyl group, a lower alkoxy group, a phenoxy group or
a halogen atom,
a phenyl group which may be optionally substituted with a lower alkyl group, a lower alkoxy group or a phenoxy group,
First, a description will be made to the optically active salicylideneaminoalcohol compound of formula (1) as defined above.
Examples of the alkyl group which may be substituted with a group selected from an alkoxy group, an aralkyloxy group, an aryloxy group, and a cycloalkoxy group, represented by R1, include
a (C1-C8)alkyl group (e.g., a methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, t-butyl, n-pentyl, n-hexyl, n-pentyl, n-octyl, n-nonyl, or n-decyl group) which may be substituted with a group selected from a (C1-C4)alkoxy group (e.g., a methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, sec-butoxy, or t-butoxy group),
a (C7-C11)aralkyloxy group (e.g., a benzyloxy, or naphthylmethyloxy group),
a (C6-C11)aryloxy group (e.g., a phenoxy, or naphthoxy group) and
a (C4-C6)cycloalkoxy group (e.g., cyclobutyloxy, cyclopentyloxy, cyclohexyloxy group).
Examples of the aralkyl group, the aryl group, and the cycloalkyl group, all of which may be substituted with a group selected from an alkyl group, an alkoxy group, an aralkyloxy group, an aryloxy group, and a cycloalkoxy group include
a (C7-C11)aralkyl group (e.g., a benzyl, or naphthylmethyl group),
a (C6-C10)aryl group(e.g., a phenyl, or naphthyl group,
a (C4-C6)cycloalkyl group(e.g., a cyclobutyl, cyclopentyl, or cyclohexyl group), all of which may be substituted with a group as specified above.
The alkyl group represented by R2 has the same meanings as defined above for the (C1-C8)alkyl group.
The cycloalkyl group, and the aralkyl or phenyl group which may be substituted with a group selected from an alkyl group, an alkoxy group, an aralkyloxy group, an aryloxy group and a cycloalkoxy group represented by R2 have the same meanings as defined above for R1.
Among the optically active salicylideneaminoalcohol compound of formula (1), R1 and R2 are preferably an alkyl group (e.g. lower alkyl groups having 1 to 4 carbon atoms such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, tert-butyl group or the like), an aralkyl group (e.g., a benzyl group), an aryl group (e.g., a phenyl group, a 2-methoxyphenyl group, a 2-tert-butoxy-5-tert-butylphenyl group or a 2-octyloxy-5-tert-butylphenyl group).
Specific examples the optically active salicylideneaminoalcohol compound of formula (1) include optically active N-(3-fluorosalicyliden)-2-amino-1,1-di(2-butoxy-5-t-butylphenyl)-1-propanol, N-(3-fluorosalicyliden)-2-amino-1,1-di(2-octyloxy-5-t-butylphenyl)-1-propanol, N-(3-fluorosalicyliden)-2-amino-1,1-di(2-butoxy-5-t-butylphenyl)-3-phenyl-1-propanol, N-(3-fluorosalicyliden)-2-amino-1,1-di(2-methoxyphenyl)-1-propanol, N-(3-fluorosalicyliden)-2-amino-1,1-diphenyl-1-propanol, N-(3-fluorosalicyliden)-2-amino-1,1-di(2-benzyloxy-5-methylphenyl)-3-(4-isopropoxyphenyl)-1-propanol, N-(3-fluorosalicyliden)-2-amino-1,1-diphenyl-3-phenyl-1-propanol, N-(3-fluorosalicyliden)-2-amino-1,1-di(2-methoxyphenyl)-3-methyl-1-butanol, N-(3,5-dichlorosalicylidene)-2-amino-1,1-diphenyl-1-propanol, N-(3,5-dichlorosalicylidene)-2-amino-1,1-di-(2-methoxyphenyl)-1-propanol N-(3,5-dichlorosalicylidene)-2-amino-1,1-di(5-tert-butyl-2-tert-butoxyphenyl)-3-phenyl-1-propanol, N-(3,5-dichlorosalicylidene)-2-amino-1,1-di-(5-tert-butyl-2-octyloxyphenyl)-1-propanol N-(3,5-dichlorosalicylidene)-2-amino-1,1-di(2-methoxyphenyl)-3-methyl-1-butanol, N-(5-nitrosalicyliden)-2-amino-1,1-diphenyl-1-propanol, N-(5-nitrosalicyliden)-2-amino-1,1-diphenyl-3-phenyl-1-propanol, N-(5-nitrosalicyliden)-2-amino-1,1-di(2-butoxy-5-t-butylphenyl)-3-phenyl-1-propanol, N-(5-nitrosalicyliden)-2-amino-1,1-di(2-benzyloxy-5-methylphenyl)-3-(4-isopropoxyphenyl)-1-propanol, N-(5-nitrosalicyliden)-2-amino-1,1-di(2-methoxyphenyl)-1-propanol, N-(5-nitrosalicyliden)-2-amino-1,1-di(2-t-butyl-4-methylphenyl)-3-phenyl-1-propanol, N-(5-nitrosalicyliden)-2-amino-1,1-di(4-t-butylphenyl)-1-propanol, N-(5-nitrosalicyliden)-2-amino-1,1-di(2-methoxyphenyl)-3-methyl-1-propanol, N-(5-nitrosalicylidene)-2-amino-1,1-di-(5-tert-butyl-2-octyoxyphenyl)-1-propanol, N-(5-nitrosalicylidene)-2-amino-1,1-di(5-tert-butyl-2-tert-butoxyphenyl)-3-phenyl-1-propanol, N-(5-nitrosalicylidene)-2-amino-1,1-di(5-tert-butyl-2-tert-butoxyphenyl)-3-methyl-1-butanol and the like. Said optically active compounds have either an S configuration or R configuration with respect to the carbon atom denoted by xe2x80x9c*xe2x80x9d in the formula above.
Next, a description will be made to the process for producing the optically active salicylideneaminoalcohol compound of formula (1) comprising reacting an optically active amino alcohol of formula (2) with a salicylaldehyde derivative of formula (3) as defined above.
The optically active amino alcohol compound of formula (2) to be used in this process include those having R1 and R2 groups as specified above and specific examples thereof include optically active 2-amino-1,1-diphenyl-1-propanol, 2-amino-1,1-di(2-methoxyphenyl)-1-propanol, 2-amino-1,1-di(2-isopropoxyphenyl)-1-propanol, 2-amino-1,1-di(2-butoxy-5-t-butylphenyl)-1-propanol, 2-amino-1,1-diphenyl-3-phenyl-1-propanol, 2-amino-1,1-di(2-methoxyphenyl)-3-phenyl-1-propanol, 2-amino-1,1-di(2-isopropoxyphenyl)-3-phenyl-1-propanol, 2-amino-1,1-di(2-butoxy-5-t-butylphenyl)-3-phenyl-1-propanol, 2-amino-1,1-di(2-methoxyphenyl)-3-phenyl-1-butanol, 2-amino-1,1-di(2-butoxy-5-t-butylphenyl)-1-propanol, 2-amino-1,1-di(2-octyloxy-5-t-butylphenyl)-1-propanol, 2-amino-1,1-di(2-butoxy-5-t-butylphenyl)-3-phenyl-1-propanol, 2-amino-1,1-di(2-methoxyphenyl)-1-propanol, 2-amino-1,1-di(2-benzyloxy-5-methylphenyl)-3-(4-isopropoxyphenyl)-1-propanol, 2-amino-1,1-di(2-methoxyphenyl)-3-methyl-1-butanol, 2-amino-1,1-di(2-t-butyl-4-methylphenyl)-3-phenyl-1-propanol, 2-amino-1,1-di(4-t-butylphenyl)-1-propanol, 2-amino-1,1-di(2-methoxyphenyl)-3-methyl-1-propanol and the like.
The reaction of the optically active amino alcohol (2) with the salicylaldehyde derivative (3) is usually conducted at 20 to 150xc2x0 C., preferably 50 to 120xc2x0 C.
Said reaction is usually conducted by contacting the optically active amino alcohol with the slicylaldehyde derivative (3) in an organic solvent, examples of which include
an aromatic hydrocarbon solvent such as toluene, xylene or the like,
a halogenated hydrocarbon solvent such as chlorobenzene, dichloromethane, dichloroethane or the like,
an alcohol solvent such as methanol or the like,
an aliphatic hydrocarbon such as hexane, heptane, cyclohexane or the like,
an ether such as diethylether, methyl-t-butylether or the like, an ester such as methyl acetate, ethyl acetate or the like, and a mixture thereof. An amount thereof to be used is not particularly limited.
An amount of the slicylaldehyde derivative to be used is usually 1 to 2 moles, preferably 1 to 1.5 moles per mol of the optically active amino alcohol of formula (2).
The salicylidenaminoalcohol of formula (1) is usually contacted with a mon-valent or di-valent copper compound to produce a chiral copper complex in a solvent.
Examples of the mono-valent or di-valent copper compound include
a copper salt of an organic carboxylic acid having 2 to 15 carbon atoms such as copper acetate, copper naphthenate, copper octanoate and the like, and
a copper salt such as copper chloride, copper bromide, copper nitrate, copper sulfate, copper methanesulfonte, copper trifluoromethanesulfonate, copper cyanate, or copper carbonate, and copper oxide, and a mixture thereof.
Examples of the solvent include a halogenated hydrocarbon such as dichloromethane, dichloroethane, chloroform, carbon tetrachloride or the like, and an aromatic hydrocarbon such as toluene, xylene or the like, an ether such as diethylether, methyl-t-butylether or the like, an ester such as methyl acetate, ethyl acetate or the like, and a mixture thereof. An amount thereof to be used is not particularly limited and is usually 2 to 500 parts by weight per 1 part by weight of the copper compound. Prochiral olefins of formula (6) to be used in the next cyclopropanation step may also be used as a solvent.
An amount of the optically active salicylideneaminoalcohol compound of formula (1) to be used is usually 0.5 to 5 moles, preferably 0.8 to 2.5 moles per mol of the copper compound. The reaction temperature is usually 10 to 120xc2x0 C., preferably 20 to 100xc2x0 C.
After completion of the reaction, the resulting reaction mixture containing the desired chiral copper complex may be used as it is in a solution form in the subsequent cyclopropanation reaction, or it may be washed with an aqueous alkali solution (e.g, aqueous solution of sodium hydrogencarbonate, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate or the like) and the evaporated to give the desired chiral copper complex.
Alternatively the desired copper complex can be precipitated as a green colored crystal by cooling the reaction solution at a temperature of ranging from xe2x88x9250 to +30xc2x0 C., preferably xe2x88x9210 to 20xc2x0 C.
The copper complex may be also precipitated from the reaction solution by the addition of an aliphatic hydrocarbon solvent (e.g., hexane or heptane). The amount of the solvent to be used is 0.05 to 50 parts by weight, preferably 0.5 to 500 parts by weight per 1 part by weight of the solvent used for the preparation of the complex as above. After the addition of the solvent, the resulting mixture may be cooled thereafter to a temperature of 0 to 30xc2x0 C.
Said precipitated crystals of the chiral copper complex can be separated by filtration from the reaction mixture, and collected crystals may be further washed with said aliphatic or aromatic hydrocarbon solvent (e.g., an aromatic or aliphatic hydrocarbon solvent such as toluene, hexane, heptane or the like), if necessary. The separated crystal can be subjected to high-performance liquid chromatography or elemental analysis to calculate the yield or purity thereof.
The chiral copper complex can form an adduct with a prochiral olefin of formula (5). Said adduct can be obtained by contacting the isolated chiral copper complex with the prochiral olefin of formula (5) or by using the prochiral olefin as a solvent to produce the chiral copper complex. The adduct can be used as a catalyst in the cyclopropanation reaction.
The chiral copper complex having an optically active salicylideneaminoalcohol compound of formula (1) wherein R1 and R2 are the same or different and independently represent an alkyl group, an aralkyl group, a phenyl group, a 2-methoxyphenyl group, a 2-tert-butoxy-5-tert-butylphenyl group or a 2-octyloxy-5-tert-butylphenyl group, and X1 represents a nitro group and X2 is a hydrogen atom, X1 represents a chlorine atom and X2 is a chlorine atom, or X1 represents a hydrogen atom and X2 is a fluorine atom as shown by formula (1)xe2x80x2 above can be obtained in a crystal form.
A description will be made to the process for producing optically active cyclopropanecarboxylic acid ester of formula (4) as defined above comprising reacting a prochiral olefin of formula (5) with a diazoacetic acid ester of formula (6) in the presence of a chiral copper complex thus obtained.
Examples of the alkoxy group represented by R3, R4, R5 or R6 of the prochiral olefin include an alkoxy group having 1 to 3 carbon atoms such as a methoxy, ethoxy, n-propoxy, i-propoxy, or the like.
Examples of the alkyl group which may be substituted with a halogen atom or an alkoxy group include
a linear or branched alkyl group having 1 to 10 carbon atoms such as a methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, or n-decyl group,
an alkyl group substituted with a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom and the like a haloalkyl group such as a chloromethyl, dichloromethyl, trichloromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trichloroethyl group or the like),
an alkyl group substituted with an alkoxy group such as a methoxy, ethoxy, n-propoxy, i-propoxy group or the like.
Examples of the alkylene group formed by R3 and R4, or R5 and R6 include an alkylene group having 2 to 4 carbon atoms such as dimethylnene, trimethylene, or tetramethylene group.
Examples of the alkenyl group which may be substituted with a halogen atom, an alkoxy group or an alkoxy carbonyl group, of which alkoxy may be substituted with a halogen atom or atoms, represented by R3, R4, R5 include
a linear or branched alkenyl groups having 1 to 10 carbon atoms such as an ethenyl, propenyl, 2-methylpropenyl, 1-butenyl, 2-butenyl, or hexenyl group,
a haloalkenyl group, which is the above-described alkenyl group substituted with the above-described halogen atom or atoms, such as a chloroethenyl group, a chloropropenyl group, 2,2-dichloroethenyl group, 2,2-difluoroethenyl group or the like,
an alkoxy(C1-C3)carbonyl substituted alkenyl group such as 2-methoxycarbonyl-2-methylethenyl group, 2-ethoxycarbonyl-2-methylethenyl group, 2-(1,1,1,3,3,3-hexafluoroisopropoxycarbonyl)-1-methylethenyl group or the like.
Specific examples of the prochiral olefin (5) include propene, 1-butene, isobutylene, 1-pentene, 1-hexene, 1-octene, 4-chloro-1-butene, 1-chloro-2-methylpropene, 2-pentene, 2-heptene, 2-methyl-2-butene, 2,5-dimethyl-2,4-hexadiene, 2-chloro-5-methyl-2,4-hexadiene, 2-fluoro-5-methyl-2,4-hexadiene, 1,1,1-trifluoro-5-methyl-2,4-hexadiene, 1,1,1-trifluoro-2-chloro-5-methyl-2,4-hexadiene, 2-methoxycarbonyl-5-methyl-2,4-hexadiene, 2-ethoxycarbonyl-5-methyl-2,4-hexadiene, 1,1-difluoro-4-methyl-1,3-pentadiene, 1,1-dichloro-4-methyl-1,3-pentadiene, 1,1-dichloro-2,4-dimethyl-1,3-pentadiene, 2-methyl-2,4-hexadiene, 2,3-dimethyl-2-pentene, 1,1,1-trichloro-4-methyl-3-pentene and the like. 1,1-dibromo-4-methyl-1,3-pentadiene, 1-chloro-1-fluoro-4-methyl-1,3-pentadiene, 1-chloro-1-(4-chlorophenyl)-4-methyl-1,3-pentadiene, 1-fluoro-1-bromo-4-methyl-1,3-pentadinene, 2-(1,1,1,3,3,3-hexafluoroisopropoxycarbonyl)-5-methyl-2,4-hexadiene, 1-methoxy-4-methyl-1,3-pentadiene, 1-ethoxy-4-methyl-1,3-pentadiene, 1-propoxy-4-methyl-1,3-pentadiene, 1-fluoro-1-methoxy-4-methyl-1,3-pentadiene, 1-fluoro-1-ethoxy-4-methyl-1,3-pentadiene, 1-fluoro-1-propoxy-4-methyl-1,3-pentadiene, 1,1,1-tribromo-4-methyl-3-pentene, 2-bromo-2,2-dimethyl-4-hexene, 2-chloro-2,5-dimethyl-4-hexene, 1-methoxy-2-methyl-1-propene, 1-ethoxy-2-methyl-1-propene, 1-propoxy-2-methyl-1-propene, 1-methoxy-8-methyl-2-butene, 1-ethoxy-3-methyl-2-butene, 1-propoxy-3-methyl-2-butene, 1,1-dimethoxy-3-methyl-2-butene, 1,1-diethoxy-3-methyl-2-butene, isopropylidenecyclopropane, isopropylidenecyclobutane, 2-methyl-4-cyclopenthylidene-2-buten, isopropylidenecyclopentane and the like.
Preferably, R3 and R4, or R5 and R6 represent a methyl group. More preferred prochiral olefins are isobutylene and 2,5-dimethyl-2,4-hexadiene.
Examples of the alkyl group having 1 to 8 carbon atoms represented by R7 in the diazoacetic acid ester of formula (6) include
a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a n-pentyl group, a n-hexyl group, a n-octyl group and the like.
Examples of the cycloalkyl group which may be optionally substituted with a lower alkyl group include a cyclohexyl group, a 1-menthyl group, a d-menthyl group, an adamantyl group.
Examples of the phenyl group which may be optionally substituted with a lower alkyl group, a lower alkoxy group or a phenoxy group represented by R7 in formula (6) include a phenyl group, 2-methylphenyl group, 3,5-dimethylphenyl group, 4-methyl-2,6-di-tert-butylphenyl group, 2-methoxyphenyl group, 3,5-dimethoxyphenyl group and the like.
Examples of the benzyl group which may be optionally substituted with a lower alkyl group, a lower alkoxy group, a phenoxy group or a halogen atom, represented by R7 in formula (6) include a 3-phenoxybenzyl group, 2-methyl-3-phenylbenzyl group, 2,3,5,6-tetrafluorobenzyl group, 2,3,5,6-tetrafluoro-4-methylbenzyl group and the like.
Examples of the lower alkyl group which may be present on the cycloalkyl group or on the phenyl group include a (C1-C4)alkyl group such as a methyl group, an ethyl group, a n-propyl group, an i-propyl group, a n-butyl group, an i-butyl group, a sec-butyl group, and a t-butyl group.
Examples of the lower alkoxy group which may be present on the phenyl group include a (C1-C4)alkoxyl group such as a methoxy group, an ethoxy group, a n-propoxy group, an i-propoxy group, a n-butoxy group, an i-butoxy group, a sec-butoxy group, and a t-butoxy group.
Preferred are a (C1-C6)alkyl group,
a phenyl group which may be optionally substituted with a lower alkyl group, a lower alkoxy group or a phenoxy group such as a phenyl group, 2-methylphenyl group, 3,5-dimethylphenyl group, 4-methyl-2,6-di-tert-butylphenyl group, 2-methoxyphenyl group, 3,5-dimethoxyphenyl group,
a cyclohexyl group, a 1-menthyl group, a d-menthyl group, and
2,3,5,6-tetrafluorobenzyl group and 3-phenoxybenzyl group.
Specific examples of the diazoacetic acid ester of formula (6) include ethyl diazoacetate, n-propyl diazoacetate, tert-butyl diazoacetate, phenyl diazoacetate, 1-menthyl diazoacetate, 4-methyl-2,6-di-tert-butylphenyl diazoacetate, 2,3,5,6-tetrafluorobenzyl diazoacetate, 3-phenoxybenzyl diazoacetate and the like.
Said diazoacetic esters of formula (6) is commercially available or may be prepared by the known method such as a method of reacting corresponding amino acid esters with a diazotizing agent prepared from sodium nitrite and mineral acids may be used.
The reaction of prochiral olefin of formula (5) with diazoacetic esters of formula (6) in the presence of the prepared chiral copper complex catalyst is usually performed by adding the diazoacetic ester of formula (6) to a mixture of the copper complex catalyst and the prochiral olefin of (5) and optionally in a solvent. As described above, the present reaction may be performed in the presence of a reducing agent such as phenylhydrazine or the like.
An amount of prochiral olefin of formula (5) to be used is usually 1 or mole or more per mol of the diazoacetic acid ester of formula (6). The upper limit thereof is not particularly limited and, for example, a large excess amount may be used so as to serve as a reaction solvent.
An amount of the copper complex catalyst to be used is usually 0.001 to 5 mole %, preferably 0.03 to 1 mole % in terms of copper relative to the diazoacetic ester of formula (6).
Examples of the solvent to be used include a halogenated hydrocarbon such as 1,2-dihloroethane, chloroform, carbon tetrachloride or the like,
an aliphatic hydrocarbon such as hexane, heptane, cyclohexane and the like,
an aromatic hydrocarbon such as benzene, toluene, xylene and the like,
an ester such as methyl acetate, ethyl acetate and the like, and a mixture thereof. Alternatively, the prochiral olefin (5) may be used as a solvent.
An amount of a solvent to be used is usually 2 to 50 parts by weight, preferably 3 to 30 parts by weight per 1 part by weight of the diazoacetic ester (6).
A reaction temperature is usually xe2x88x9220 to 150xc2x0 C., preferably xe2x88x9210 to 120xc2x0 C. In addition, the reaction is usually performed under an inert gas atmosphere such as a nitrogen gas or the like and the inert gas may contain, for example, 5% or less oxygen gas. In addition, the reaction can be conducted in the presence of excess amount of peroxide, for example, 20 moles or less, preferably 10 moles or less of peroxide per mol of the copper complex in the reaction without accompanying substantial adverse effect.
After completion of the reaction, the optically active cyclopropanecarboxylic acid ester derivative of formula (4) can be separated by distillation or the like, which may be further subjected to ester hydrolysis or the like, or may be further purified, for example, by distillation, column chromatography or the like, if necessary.
Examples of the optically active cyclopropanecarboxylic acid esters of formula (4) include optically active methyl 2-methylcyclopropanecarboxylate, ethyl 2-methylcyclopropanecarboxylate, n-propyl 2-methylcyclopropanecarboxylate, isopropyl 2-methylcyclopropanecarboxylate, isobutyl 2-methylcyclopropanecarboxylate, tert-butyl 2-methylcyclopropanecarboxylate, cyclohexyl 2-methylcyclopropanecarboxylate, menthyl 2-methylcyclopropanecarboxylate, (4-methyl-2,6-di-tert-butylphenyl) 2-methylcyclopropanecarboxylate, methyl 2,2-dimethylcyclopropanecarboxylate, ethyl 2,2-dimethylcyclopropanecarboxylate, n-propyl 2,2-dimethylcyclopropanecarboxylate, isopropyl 2,2-dimethylcyclopropanecarboxylate, isobutyl 2,2-dimethylcyclopropanecarboxylate, tert-butyl 2,2-dimethylcyclopropanecarboxylate, cyclohexyl, 2,2-dimethylcyclopropanecarboxylate, menthyl 2,2-dimethylcyclopropanecarboxylate, (4-methyl-2,6-di-tert-butylphenyl) 2,2-dimethylcyclopropanecarboxylate, methyl 2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate, ethyl 2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate, n-propyl 2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate, isopropyl 2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate, isobutyl 2,2-dimethyl-3-(3-methyl-1-propenyl)cyclopropanecarboxylate, tert-butyl 2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate, cyclohexyl 2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate, menthyl 2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate, (4-methyl-2,6-di-tert-butylphenyl) 2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate, (3-phenoxybenzyl) 2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate, (2,3,5,6-tetrafluoro-4-methoxymethylbenzyl) 2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate, methyl 2,2-dimethyl-3-(2,2-dichloro-1-ethenyl)cyclopropanecarboxylate, ethyl 2,2-dimethyl-3-(2,2-dichloro-1-ethenyl)cyclopropanecarboxylate, n-propyl 2,2-dimethyl-3-(2,2-dichloro-1-ethenyl)cyclopropanecarboxylate, isopropyl 2,2-dimethyl-3-(2,2-dichloro-1-ethenyl)cyclopropanecarboxylate, isobutyl 2,2-dimethyl-3-(2,2-dichloro-1-ethenyl)cyclopropanecarboxylate, tert-butyl 2,2-dimethyl-3-(2,2-dichloro-1-ethenyl)cyclopropanecarboxylate, cyclohexyl 2,2-dimethyl-3-(2,2-dichloro-1-ethenyl)cyclopropanecarboxylate, menthyl 2,2-dimethyl-3-(2,2-dichloro-1-ethenyl)cyclopropanecarboxylate, (4-methyl-2,6-di-tert-butylphenyl) 2,2-dimethyl-3-(2,2-dichloro-1-ethenyl)cyclopropanecarboxylate, (3-phenoxybenzyl) 2,2-dimethyl-3-(2,2-dichloro-1-ethenyl)cyclopropanecarboxylate, (2,3,5,6-tetrafluoro-4-methoxymethylbenzyl) 2,2-dimethyl-3-(2,2-dichloro-1-ethenyl)cyclopropanecarboxylate, ethyl 2,2-dimethyl-3-(2,2-dibromo-1-ethenyl)cyclopropanecarboxylate, methyl 2,2-dimethyl-3-(2,2,2-trichloroethyl)cyclopropanecarboxylate, ethyl 2,2-dimethyl-3-(2,2,2-trichloroethyl)cyclopropanecarboxylate, n-propyl 2,2-dimethyl-3-(2,2,2-trichloroethyl)cyclopropanecarboxylate, isopropyl 2,2-dimethyl-3-(2,2,2-trichloroethyl)cyclopropanecarboxylate, isobutyl 2,2-dimethyl-3-(2,2,2-trichloroethyl)cyclopropanecarboxylate, tert-butyl 2,2-dimethyl-3-(2,2,2-trichloroethyl)cyclopropanecarboxylate, cyclohexyl 2,2-dimethyl-3-(2,2,2-trichloroethyl)cyclopropanecarboxylate, menthyl 2,2-dimethyl-3-(2,2,2-trichloroethyl)cyclopropanecarboxylate, (4-methyl-2,6-di-tert-butylphenyl) 2,2-dimethyl-3-(2,2,2-trichloroethyl)cyclopropanecarboxylate (3-phenoxybenzyl) 2,2-dimethyl-3-(2,2,2-trichloroethyl)cyclopropanecarboxylate, (2,3,5,6-tetrafluoro-4-methoxymethylbenzyl) 2,2-dimethyl-3-(2,2,2-trichloroethyl)cyclopropanecarboxylate, methyl 2,2-dimethyl-3-(2-carboethoxy-1-propenyl)cyclopropanecarboxylate, ethyl 2,2-dimethyl-3-(2-carbomethoxy-1-propenyl)cyclopropanecarboxylate, n-propyl 2,2-dimethyl-3-(2-carboethoxy-1-propenyl)cyclopropanecarboxylate, isopropyl 2,2-dimethyl-3-(2-carbomethoxy-1-propenyl)cyclopropanecarboxylate, isobutyl 2,2-dimethyl-3-(2-carboethoxy-1-propenyl)cyclopropanecarboxylate, tert-butyl 2,2-dimethyl-3-(2-carbomethoxy-1-propenyl)cyclopropanecarboxylate, cyclohexyl 2,2-dimethyl-3-(2-carboethoxy-1-propenyl)cyclopropanecarboxylate, menthyl 2,2-dimethyl-3-(2-carbomethoxy-1-propenyl)cyclopropanecarboxylate, 4-methyl-2,6-di-tert-butylphenyl 2,2-dimethyl-3-(2-carboethoxy-1-propenyl)cyclopropanecarboxylate (3-phenoxybenzyl) 2,2-dimethyl-3-(2-carbomethoxy-1-propenyl)cyclopropanecarboxylate, (2,3,5,6-tetrafluoro-4-methoxymethylbenzyl) 2,2-dimethyl-3-(2-carboethoxy-1-propenyl)cyclopropane-carboxylate, ethyl 2,2-dimethyl-3-(2-chloro-2-(4-chloropenyl)-1-ethenyl)cyclopropanecarboxylate, ethyl 2,2-dimethyl-3-(2-chloro-2-trifluoromethyl-1-ethenyl)cyclopropanecarboxylate and the like.
The optically active salicylideneaminoalcohol compound of formula (1) contained in the residue after isolating the optically active cyclopropanecarboxylic acid ester derivative of formula (4) can be recovered by subjecting the residue to crystallization treatment, column chromatography or the like.